Work the stage: myocardial work and aortic valve stenosis cardiac damage staging independently predict all-cause mortality in patients undergoing transcatheter aortic valve replacement

Abstract In aortic stenosis (AS) chronic left ventricular (LV) pressure overload and its backward effects result in significant cardiopulmonary remodeling. The classification of this extravalvular cardiac damage serves as a comprehensive marker of disease severity. Notably, the evaluation of LV function is challenging due to the substantial influence of the increased afterload on conventional echocardiographic parameters. Myocardial work (MW) analysis integrates myocardial deformation with instantaneous LV pressure, providing a more accurate representation of LV contractility. Both cardiac damage staging and MW assessment may offer significant prognostic value in the clinically complex patients undergoing transcatheter aortic valve replacement (TAVR), therefore we aimed to assess their association with patients’ outcomes. 319 TAVR candidates (79±6 years, 40% female) were enrolled. After a detailed preprocedural echocardiographic exam we determined the extent of cardiac damage associated with AS: patients were classified as Stage 0 (no cardiac damage), Stage 1 (LV damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (pulmonary artery vasculature or tricuspid valve damage), or Stage 4 (right ventricular damage). We also measured LV ejection fraction (EF) and global longitudinal strain (GLS). Global myocardial work index (GWI) was calculated using dedicated software and LV pressure was estimated using transaortic mean gradient and systolic blood pressure. Our primary outcome was all-cause mortality, reached by 78 patients during a median follow-up of 29 months. In our cohort 14 (4%) patients were classified as Stage 0, 60 (19%) as Stage 1, 149 (47%) as Stage 2, 21 (7%) as Stage 3, and 75 (24%) as Stage 4. Preoperative GWI values showed a continuous decrease through the AS cardiac damage Stages (from Stage 0-4: 2542±497 vs. 2404±378 vs. 2006±602 vs. 1690±939 vs. 1064±290 mmHg%; p0.001). Using univariate Cox analysis GWI (HR 0.963 95% CI 0.932-0.994 per 100-unit change; p=0.020) and AS Staging (HR 1.236 95% CI 1.022-1.495; p=0.029) showed stronger association with all-cause mortality than EF (HR 0.983 95% CI 0.966-1.000; p=0.046) or GLS (HR 1.052 95% CI 0.997-1.110; p=0.063). In a multivariable Cox regression model, GWI (HR 0.955 95% CI 0.917-0.995 per 100-unit change; p=0.028) and AS Staging (HR 1.289 95% CI 1.005-1.654; p=0.046) were both independent predictors of all-cause mortality along with sex, diabetes mellitus, chronic obstructive pulmonary disease, tricuspid annular plane systolic excursion and LV end-diastolic volume. In the fragile, multimorbid cohort of TAVR patients, preoperative GWI values demonstrated a progressive decline across the AS Stages. Additionally, GWI had higher prognostic value than conventional measures of LV function. Moreover, GWI and AS cardiac damage Staging proved to be strong independent predictors of all-cause mortality, underpinning their additional value in this clinically complex population.